tbuckley/cabot-search huggingface dataset:
Comparison of microstructure, mechanical property, and degradation rate of Mg–1Li–1Ca and Mg–4Li–1Ca alloys
Authors: Li-Xin Long, Fen-Fen Chen, Lan-Yue Cui, Ze-Song Wei, Hai-Tao Wang, Rong-Chang Zeng, Yu-Feng Zheng
Journal: Bioactive Materials (2023)

Mg-1 wt.% Li-1 wt.% Ca (LX11) and Mg-4 wt.% Li-1 wt.% Ca (LX41) alloys share the same hexagonal closed-packed crystalline structure. However, the differences in microstructure, mechanical properties, and degradation rates between the two alloys are not well understood. Hereby, the above three aspects of LX11 and LX41 alloys were studied via optical microscopy, tensile tests, and electrochemical polarization and electrochemical impedance spectroscopy, together with hydrogen evolution. The concentration of the released Mg2+, Ca2+, and Li+ ions was analyzed using a flame atomic absorption spectrophotometer. Results demonstrated that the LX11 alloy was composed of finer α-Mg grains, fewer twins, and smaller volume fractions of the intermetallic phases Mg2Ca than the LX41 alloy. The increasing Li concentration generated a weak decrease in the yield strength of the Mg-Li-Ca alloys, a remarkable increase in elongation to failure, and a stable ultimate tensile strength. The LX11 alloy had better corrosion resistance than the LX41 alloy. The release rate of the cations (Mg2+, Ca2+, and Li+) varied significantly with time. The release rate of metallic ions in Hank's solution cannot reflect the true corrosion rate of Mg-Li-Ca alloys due to the formation of the precipitated corrosion products and their difference in solubility. The dealloying corrosion mechanism of the Mg2Ca phase in Mg-Li-Ca alloys was proposed.
Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance
Authors: Saeko Yamada, Yasuo Nagafuchi, Min Wang, Mineto Ota, Hiroaki Hatano, Yusuke Takeshima, Mai Okubo, Satomi Kobayashi, Yusuke Sugimori, Nakano Masahiro, Ryochi Yoshida, Norio Hanata, Yuichi Suwa, Yumi Tsuchida, Yukiko Iwasaki, Shuji Sumitomo, Kanae Kubo, Kenichi Shimane, Keigo Setoguchi, Takanori Azuma, Hiroko Kanda, Hirofumi Shoda, Xuan Zhang, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio
Journal: Annals of the Rheumatic Diseases (2023)

Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance.We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis.Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s.An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.
Conservation and divergence of canonical and non-canonical imprinting in murids
Authors: Julien Richard Albert, Toshihiro Kobayashi, Azusa Inoue, Ana Monteagudo-Sánchez, Soichiro Kumamoto, Tomoya Takashima, Asuka Miura, Mami Oikawa, Fumihito Miura, Shuji Takada, Masumi Hirabayashi, Keegan Korthauer, Kazuki Kurimoto, Maxim V. C. Greenberg, Matthew Lorincz, Hisato Kobayashi
Journal: Genome biology (2023)

Abstract Background Genomic imprinting affects gene expression in a parent-of-origin manner and has a profound impact on complex traits including growth and behavior. While the rat is widely used to model human pathophysiology, few imprinted genes have been identified in this murid. To systematically identify imprinted genes and genomic imprints in the rat, we use low input methods for genome-wide analyses of gene expression and DNA methylation to profile embryonic and extraembryonic tissues at allele-specific resolution. Results We identify 14 and 26 imprinted genes in these tissues, respectively, with 10 of these genes imprinted in both tissues. Comparative analyses with mouse reveal that orthologous imprinted gene expression and associated canonical DNA methylation imprints are conserved in the embryo proper of the Muridae family. However, only 3 paternally expressed imprinted genes are conserved in the extraembryonic tissue of murids, all of which are associated with non-canonical H3K27me3 imprints. The discovery of 8 novel non-canonical imprinted genes unique to the rat is consistent with more rapid evolution of extraembryonic imprinting. Meta-analysis of novel imprinted genes reveals multiple mechanisms by which species-specific imprinted expression may be established, including H3K27me3 deposition in the oocyte, the appearance of ZFP57 binding motifs, and the insertion of endogenous retroviral promoters. Conclusions In summary, we provide an expanded list of imprinted loci in the rat, reveal the extent of conservation of imprinted gene expression, and identify potential mechanisms responsible for the evolution of species-specific imprinting.
Programmed and environmental determinants driving neonatal mucosal immune development
Authors: Natalia Torow, Timothy W. Hand, Mathias W. Hornef
Journal: Immunity (2023)

The mucosal immune system of neonates goes through successive, non-redundant phases that support the developmental needs of the infant and ultimately establish immune homeostasis. These phases are informed by environmental cues, including dietary and microbial stimuli, but also evolutionary developmental programming that functions independently of external stimuli. The immune response to exogenous stimuli is tightly regulated during early life; thresholds are set within this neonatal "window of opportunity" that govern how the immune system will respond to diet, the microbiota, and pathogenic microorganisms in the future. Thus, changes in early-life exposure, such as breastfeeding or environmental and microbial stimuli, influence immunological and metabolic homeostasis and the risk of developing diseases such as asthma/allergy and obesity.
Pre-existing Fc profiles shape the evolution of neutralizing antibody breadth following influenza vaccination
Authors: Carolyn M. Boudreau, John S. Burke, Alexander L. Roederer, Matthew J. Gorman, Sophia Mundle, Daniel Lingwood, Simon Delagrave, Saranya Sridhar, Ted M. Ross, Harry Kleanthous, Galit Alter
Journal: Cell Reports Medicine (2023)

Under the ever-present threat of a pandemic influenza strain, the evolution of a broadly reactive, neutralizing, functional, humoral immune response may hold the key to protection against both circulating and emerging influenza strains. We apply a systems approach to profile hemagglutinin- and neuraminidase-specific humoral signatures that track with the evolution of broad immunity in a cohort of vaccinated individuals and validate these findings in a second longitudinal cohort. Multivariate analysis reveals the presence of a unique pre-existing Fcγ-receptor-binding antibody profile in individuals that evolved broadly reactive hemagglutination inhibition activity (HAI), marked by the presence of elevated levels of pre-existing FCGR2B-binding antibodies. Moreover, vaccination with FCGR2B-binding antibody-opsonized influenza results in enhanced antibody titers and HAI activity in a murine model. Together, these data suggest that pre-existing FCGR2B binding antibodies are a key correlate of the evolution of broadly protective influenza-specific antibodies, providing insight for the design of next-generation influenza vaccines.
Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery
Authors: Bryan Z. Wang, Trevor R. Nash, Xiaokan Zhang, Jenny Rao, Laura Abriola, Youngbin Kim, Sergey Zakharov, Michael Kim, Lori J. Luo, Margaretha Morsink, Bohao Liu, Roberta I. Lock, Sharon Fleischer, Manuel A. Tamargo, Michael Bohnen, Carrie L. Welch, Wendy K. Chung, Steven O. Marx, Yulia V. Surovtseva, Gordana Vunjak-Novakovic, Barry M. Fine
Journal: Cell Reports Medicine (2023)

Restrictive cardiomyopathy (RCM) is defined as increased myocardial stiffness and impaired diastolic relaxation leading to elevated ventricular filling pressures. Human variants in filamin C (FLNC) are linked to a variety of cardiomyopathies, and in this study, we investigate an in-frame deletion (c.7416_7418delGAA, p.Glu2472_Asn2473delinAsp) in a patient with RCM. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with this variant display impaired relaxation and reduced calcium kinetics in 2D culture when compared with a CRISPR-Cas9-corrected isogenic control line. Similarly, mutant engineered cardiac tissues (ECTs) demonstrate increased passive tension and impaired relaxation velocity compared with isogenic controls. High-throughput small-molecule screening identifies phosphodiesterase 3 (PDE3) inhibition by trequinsin as a potential therapy to improve cardiomyocyte relaxation in this genotype. Together, these data demonstrate an engineered cardiac tissue model of RCM and establish the translational potential of this precision medicine approach to identify therapeutics targeting myocardial relaxation.
Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors
Authors: Harriet Kluger, J Carl Barrett, Justin F Gainor, Omid Hamid, Michael Hurwitz, Theresa LaVallee, Rebecca A Moss, Roberta Zappasodi, Ryan J Sullivan, Hussein Tawbi, Elad Sharon
Journal: Journal for ImmunoTherapy of Cancer (2023)

Immunotherapy is the standard of care for several cancers and the field continues to advance at a rapid pace, with novel combinations leading to indications in an increasing number of disease settings. Durable responses and long-term survival with immunotherapy have been demonstrated in some patients, though lack of initial benefit and recurrence after extended disease control remain major hurdles for the field. Many new combination regimens are in development for patients whose disease progressed on initial immunotherapy. To guide clinical trial design and support analyses of emerging molecular and cellular data surrounding mechanisms of resistance, the Society for Immunotherapy of Cancer (SITC) previously generated consensus clinical definitions for resistance to single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) in three distinct scenarios: primary resistance, secondary resistance, and progression after treatment discontinuation. An unmet need still exists, however, for definitions of resistance to ICI-based combinations, which represent an expanding frontier in the immunotherapy treatment landscape. In 2021, SITC convened a workshop including stakeholders from academia, industry, and government to develop consensus definitions for resistance to ICI-based combination regimens for improved outcome assessment, trial design and drug development. This manuscript reports the minimum drug exposure requirements and time frame for progression that define resistance in both the metastatic setting and the perioperative setting, as well as key caveats and areas for future research with ICI/ICI combinations. Definitions for resistance to ICIs in combination with chemotherapy and targeted therapy will be published in companion volumes to this paper.
Trial-of-antibiotics to assist tuberculosis diagnosis in symptomatic adults in Malawi (ACT-TB study): a randomised controlled trial
Authors: Titus H Divala, Elizabeth L Corbett, Chikondi Kandulu, Brewster Moyo, Peter MacPherson, Marriott Nliwasa, Neil French, Derek J Sloan, Lingstone Chiume, Masiye John Ndaferankhande, Sanderson Chilanga, Sabina Tazirwa Majiga, Jon Øyvind Odland, Katherine L Fielding
Journal: The Lancet Global Health (2023)
Lots of considerations when evaluating the FujiLAM assay
Authors: Alberto L Garcia-Basteiro, Frank Cobelens, Willy Ssengooba, Grant Theron
Journal: The Lancet Global Health (2023)

Point-of-care non-sputum-based tests for tuberculosis are an international research priority,1 particularly for populations for whom bacteriological confirmation is difficult, such as children or people who are immunocompromised and living with HIV. The urine-based Alere Determine TB LAM Ag (Abbott, Waltham, MA, USA) test partly meets these criteria, however, the test has important shortcomings that must be overcome.
Effects of public financing of essential maternal and child health interventions across wealth quintiles in Nigeria: an extended cost-effectiveness analysis
Authors: Wenhui Mao, David Watkins, Miriam L Sabin, Katy Huang, Etienne Langlois, Yewande Ogundeji, Helga Fogstad, Marco Schäferhoff, Gavin Yamey, Osondu Ogbuoji
Journal: The Lancet Global Health (2023)
When should global health actors prioritise more uncertain interventions?
Authors: Leah Pierson, Stéphane Verguet
Journal: The Lancet Global Health (2023)

Global health actors use economic evaluations, including cost-effectiveness analyses, to estimate the effect of different interventions they might fund. However, producing reliable cost-effectiveness estimates is difficult, meaning organisations must often choose between funding interventions for which reliable predictions of efficacy exist and those for which they do not. In practice, many organisations appear to be risk-averse, favouring more certain interventions simply because they are more certain. We argue that this practice is not justifiable. Prioritising projects backed by greater evidence might often produce greater health benefits. However, a general tendency to prefer more certain interventions will cause global health actors to overlook opportunities to help less well-studied populations, support promising but complex interventions, address the upstream causes of illness, and conduct the most important impact evaluations. We argue that global health actors should instead adopt nuanced attitudes towards uncertainty and be willing to fund highly uncertain interventions in some cases. We further describe the considerations they should take into account in rendering these judgements.
The effects of racism, social exclusion, and discrimination on achieving universal safe water and sanitation in high-income countries
Authors: Joe Brown, Charisma S Acey, Carmen Anthonj, Dani J Barrington, Cara D Beal, Drew Capone, Oliver Cumming, Kristi Pullen Fedinick, Jacqueline MacDonald Gibson, Brittany Hicks, Michal Kozubik, Nikoleta Lakatosova, Karl G Linden, Nancy G Love, Kaitlin J Mattos, Heather M Murphy, Inga T Winkler
Journal: The Lancet Global Health (2023)

Drinking water and sanitation services in high-income countries typically bring widespread health and other benefits to their populations. Yet gaps in this essential public health infrastructure persist, driven by structural inequalities, racism, poverty, housing instability, migration, climate change, insufficient continued investment, and poor planning. Although the burden of disease attributable to these gaps is mostly uncharacterised in high-income settings, case studies from marginalised communities and data from targeted studies of microbial and chemical contaminants underscore the need for continued investment to realise the human rights to water and sanitation. Delivering on these rights requires: applying a systems approach to the problems; accessible, disaggregated data; new approaches to service provision that centre communities and groups without consistent access; and actionable policies that recognise safe water and sanitation provision as an obligation of government, regardless of factors such as race, ethnicity, gender, ability to pay, citizenship status, disability, land tenure, or property rights.
Functionalization of in vivo tissue-engineered living biotubes enhance patency and endothelization without the requirement of systemic anticoagulant administration
Authors: Hongyu Yan, Quhan Cheng, Jianghua Si, Songdi Wang, Ye Wan, Xin Kong, Ting Wang, Wenting Zheng, Muhammad Rafique, Xiaofeng Li, Ju He, Adam C. Midgley, Yi Zhu, Kai Wang, Deling Kong
Journal: Bioactive Materials (2023)

Vascular regeneration and patency maintenance, without anticoagulant administration, represent key developmental trends to enhance small-diameter vascular grafts (SDVG) performance. In vivo engineered autologous biotubes have emerged as SDVG candidates with pro-regenerative properties. However, mechanical failure coupled with thrombus formation hinder translational prospects of biotubes as SDVGs. Previously fabricated poly(ε-caprolactone) skeleton-reinforced biotubes (PBs) circumvented mechanical issues and achieved vascular regeneration, but orally administered anticoagulants were required. Here, highly efficient and biocompatible functional modifications were introduced to living cells on PB lumens. The 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-methoxy (DMPE)-PEG-conjugated anti-coagulant bivalirudin (DPB) and DMPE-PEG-conjugated endothelial progenitor cell (EPC)-binding TPS-peptide (DPT) modifications possessed functionality conducive to promoting vascular graft patency. Co-modification of DPB and DPT swiftly attained luminal saturation without influencing cell viability. DPB repellent of non-specific proteins, DPB inhibition of thrombus formation, and DPB protection against functional masking of DPT's EPC-capture by blood components, which promoted patency and rapid endothelialization in rat and canine artery implantation models without anticoagulant administration. This strategy offers a safe, facile, and fast technical approach to convey additional functionalization to living cells within tissue-engineered constructs.
Delays in cancer care for children in low-income and middle-income countries: development of a composite vulnerability index
Authors: Cesia Cotache-Condor, Hannah E Rice, Kristin Schroeder, Catherine Staton, Esther Majaliwa, Shenglan Tang, Henry E Rice, Emily R Smith
Journal: The Lancet Global Health (2023)

Early access to diagnosis and care is essential to improve rates of survival from childhood cancer, particularly in low-income and middle-income countries (LMICs). Composite indices are increasingly used to compare country performance in many health fields. We aimed to develop a composite vulnerability index of risk of mortality associated with delays in care for childhood cancer in LMICs, and to compare the vulnerability index scores across countries.
Focal Xanthogranulomatous Pyelonephritis: Partial Nephrectomy as Definitive Treatment
Authors: J.M. (a) Osca, M.J. (b) Peiro, M. (a) Rodrigo, J.M. (a) Martinez-Jabaloyas, J.F. (a) Jimenez-Cruz
Journal: European Urology (1997)
Molecular Analysis of the ERGIC-53 Gene in 35 Families With Combined Factor V-Factor VIII Deficiency
Authors: M. Neerman-Arbez, K.M. Johnson, M.A. Morris, J.H. McVey, F. Peyvandi, W.C. Nichols, D. Ginsburg, C. Rossier, S.E. Antonarakis, E.G.D. Tuddenham
Journal: Blood (1999)
Comparison of Prevention Strategies for Neonatal Group B Streptococcal Infection
Authors: Janet C. Mohle-Boetani
Journal: JAMA (1993)

<h3>Background.</h3> —Intrapartum antibiotics can prevent early-onset neonatal group B streptococcal (GBS) disease but have not been widely used. Obstacles include difficulty in implementing screening for GBS colonization and uncertainty about cost-effectiveness. The GBS vaccines for disease prevention are now being developed. <h3>Methods.</h3> —We developed a decision analysis model and used standard costeffectiveness and cost-benefit analysis methods. We compared the outcomes and costs of the recent practice of no intervention with those expected for three prevention strategies: (1) intrapartum antibiotics administered to colonized women with labor complications, (2) an alternative strategy that does not require screening but uses epidemiologic criteria and labor complications to target intrapartum antibiotics, and (3) maternal vaccination. We used data from multistate population-based surveillance to estimate the potential impact of each strategy on disease and costs in the United States. <h3>Results.</h3> —Intrapartum antibiotic prophylaxis of high-risk women identified by screening could prevent approximately 3300 cases (47% of neonatal disease) annually in the United States and could save approximately $16 million in direct medical costs. Chemoprophylaxis of high-risk women identified using epidemiologic criteria could potentially be equally effective (3200 cases prevented) and would avoid the logistical difficulties of screening; the net savings would be approximately $66 million. Vaccinating 80% of pregnant women with a vaccine that prevents 80% of cases among infants born at or after 34 weeks of gestation would prevent approximately 4100 neonatal cases annually with a net savings of $131 million. <h3>Conclusions.</h3> —Universal prenatal screening for GBS and chemoprophylaxis of colonized women with labor complications is likely to be cost-beneficial in the United States. Development of alternative strategies should be further explored for populations in which GBS screening is impractical. Continued development of a GBS vaccine is an important public health priority. (<i>JAMA</i>. 1993;270:1442-1448)
Gonorrhea Screening
Authors: Anthony Adolph Luciano
Journal: JAMA (1980)

A total of 1,336 men were screened for gonococcal urethritis by one or more of three techniques: Gram-stain smears, urethral cultures, and cultures of first-voided urine (FVU). The sensitivity of these techniques in a group of 113 symptomatic patients was 99.1%, 98.2%, and 95.6%, respectively. In a group of 248 asymptomatic men, FVU cultures yielded a positivity rate of 2.4%, comparable to the 2.8% obtained with urethral cultures. In view of the reduction in time, cost, and patient discomfort associated with the use of FVU cultures, it appears to be a valuable diagnostic technique for asymptomatic gonococcal urethritis. (<i>JAMA</i>243:680-681, 1980)
Evidence and Consensus
Authors: Itzhak Jacoby
Journal: JAMA (1988)

In only ten years, the consensus conference, developed in the United States, has become important worldwide as a means of assessing the application of medical technology to clinical practice. Canada recently held its first consensus conference, on indications for cesarean section. As the article by Lomas et al<sup>1</sup>in this issue ofTHE JOURNALdescribes, research-based evidence played a critical role in this conference. The authors conclude that the evidence was well integrated into the consensus statement and that it served to modulate the degree of consensus achieved on the various issues before the conference. These conclusions prompt reflection on the role that empirical evidence has played in consensus development in the United States. See also p 3001. Donald S. Fredrickson, MD, then director of the National Institutes of Health (NIH), originated the consensus development process in 1977 with a public confirmation of the agency's responsibilities for promoting efforts